MSCs from peripheral blood; cell administration and tissue injury govern the fate of MSCs. (A) Adherent cell culture established from the peripheral blood of mobilized mice (passage 2); the cells displayed a fibroblast-like morphology as BM-derived MSCs. (B) Peripheral blood–derived MSCs (passage 6) expressed typical MSC markers as shown by flow cytometry analysis. (C) EGFP⁺ cells (green) were found in the lung directly after systemic injection of 1 × 10⁶ MSCs (passage 8) into the femoralis vein; the mouse died immediately, likely because of acute right heart failure due to obstruction of lung capillaries by MSCs. (D) EGFP⁺ cells (green) were found in the spleen 5 days after slow injection of 1.5 × 10⁶ MSCs (passage 8) into the tail vein. (E) Transplantation of 1.2 × 10⁵ enriched MSCs (passage 6, 21 days) into the intact, uninfarcted heart resulted in calcifications (black, von Kossa staining) that were clearly restricted to the injection channel. (F) Tissue damage due to the injection needle was accompanied by inflammation documented by strong invasion of hematopoietic cells (CD45 staining, white). Engraftment of MSCs (green) was limited to the lesion (injection channel); osteocalcin staining (red) proved ossification. Autofluorescence of intact cardiomyocytes appeared yellowish. Bar represents180 μm (panel A), 700 μm (panel C), 350 μm (panel D), 100 μm (panel E), 60 μm (panel F). See “Materials and Methods; Image acquisition and preparation” for microscopy details.